Early monitoring of anti-infliximab antibodies by drug-tolerant assay predicts later immunogenicity and drug survival in rheumatic diseases.

OBJECTIVES: To investigate the appearance of anti-drug antibodies (ADA) against infliximab (IFX) determined by drug-sensitive and drug-tolerant assays and their relationship with drug levels and drug survival. METHODS: This longitudinal observational study included 45 patients with rheumatoid arthritis (RA) and 61 with spondyloarthritis (SpA). Serum samples were obtained at weeks 2, 6, 12, 24, and 52. Serum IFX levels were measured by a capture enzyme-linked immunosorbent assay (ELISA) and ADA by an in-house drug-sensitive two-site (bridging) enzyme-linked immunosorbent assay (bELISA) and a commercially available drug-tolerant ELISA (IDK, Immundiagnostik, Germany). RESULTS: Anti-drug antibodies were detected earlier by IDK than by bELISA. Once ADA appeared, positivity persisted throughout the study period. Patients who were bELISA ADA+ had higher IDK ADA levels (than bELISA ADA- patients). Circulating IFX levels were detected in all patients except those found to be bELISA ADA+. Serum IFX levels were lower in IDK ADA+ than in IDK ADA-patients.Most patients (64%) discontinued due to inefficacy. The early onset of immunogenicity was related to IFX survival. Both in RA and SpA, the median survival (years) was shorter in patients with earlier development of ADA (IDK+ before or at week 24) than those who became IDK+ later (after week 24) or never developed ADA. CONCLUSION: A drug-tolerant assay detects ADA during IFX therapy earlier and more frequently than a drug-sensitive assay. The onset of immunogenicity detected by drug-tolerant assays is related to the subsequent detection of ADA by drug-sensitive assays and drug survival.

Circulating Tfh cells are differentially modified by abatacept or TNF blockers, and predict treatment response in Rheumatoid Arthritis.

OBJECTIVE: CD4+CXCR5+PD-1hi follicular helper T (Tfh) cells dwell in the germinal centers (GCs) of lymphoid organs and participate in Rheumatoid Arthritis (RA) pathogenesis; the frequency of their circulating counterparts (cTfh-frequency) is expanded in RA and correlates with the pool of GC Tfh cells. Our objective was to study the effect of abatacept (ABT) or TNF blockers (TNFb) on the cTfh-frequency in RA. METHODS: Peripheral blood was drawn from seropositive-longstanding RA patients chronically receiving csDMARDS (n = 45), TNFb (n = 59), or ABT (n = 34), and healthy controls (HC) (n = 137). Also, patients with an incomplete response to csDMARDS (n = 41) who initiated TNFb (n = 19) or ABT (n = 22), were studied at 0 and 12 months. The cTfh-frequency was examined by cytometry. RESULTS: As compared with HC, an increased cTfh-frequency was seen in seropositive-longstanding RA chronically receiving csDMARDs or TNFb but not ABT. After escalating from csDMARDs, the cTfh-frequency did not vary in patients who were given TNFb but decreased to HC levels in those given ABT. In the ABT group, the baseline cTfh-frequency was higher for patients who attained 12M remission (12Mr), vs those who remained active (12Ma): 0m cutoff for remission >0.38% (Sens. 92%, Sp. 90%), OR 25.3. Conversely, in the TNFb group, the baseline cTfh-frequency was lower for 12Mr vs 12Ma: 0m cutoff for non-remission >0.44% (Sens. 67%, Sp. 90%), OR 8.5. CONCLUSION: ABT but not TNFb, is able to curtail the cTfh-frequency in RA. A higher baseline cTfh-frequency predicts a good response to ABT but a poor response to TNFb.

Standardized nailfold capillaroscopy in children with rheumatic diseases: a worldwide study.

OBJECTIVES: To standardly assess and describe nailfold videocapillaroscopy (NVC) assessment in children and adolescents with juvenile rheumatic and musculoskeletal diseases (jRMD) vs healthy controls (HCs). MATERIAL AND METHODS: In consecutive jRMD children and matched HCs from 13 centres worldwide, 16 NVC images per patient were acquired locally and read centrally per international consensus standard evaluation of the EULAR Study Group on Microcirculation in Rheumatic Diseases. A total of 95 patients with JIA, 22 with JDM, 20 with childhood-onset SLE (cSLE), 13 with juvenile SSc (jSSc), 21 with localized scleroderma (lSc), 18 with MCTD and 20 with primary RP (PRP) were included. NVC differences between juvenile subgroups and HCs were calculated through multivariable regression analysis. RESULTS: A total of 6474 images were assessed from 413 subjects (mean age 12.1 years, 70.9% female). The quantitative NVC characteristics were significantly lower or higher in the following subgroups compared with HCs: for density: lower in jSSc, JDM, MCTD, cSLE and lSc; for dilations: higher in jSSc, MCTD and JDM; for abnormal shapes: higher in JDM and MCTD; for haemorrhages: higher in jSSc, MCTD, JDM and cSLE. The qualitative NVC assessment of JIA, lSc and PRP did not differ from HCs, whereas the cSLE and jSSc, MCTD, JDM and cSLE subgroups showed more non-specific and scleroderma patterns, respectively. CONCLUSIONS: This analysis resulted from a pioneering registry of NVC in jRMD. The NVC assessment in jRMD differed significantly from HCs. Future prospective follow-up will further elucidate the role of NVC in jRMD.

Clinical Characteristics of Juvenile Idiopathic Inflammatory Myopathy and Comparison With Adult Patients: Analysis From a Multicentric Cohort in Spain.

METHODS: This study reviewed the medical records of patients from the REMICAM cohort, a multicentric longitudinal study carried out in patients with IIM, followed up between 1980 and 2014 in 12 hospitals in Madrid, Spain. Patients with definite or probable JPM, JDM, adult DM, and adult PM according to the modified Bohan and Peter criteria were selected. We compared the characteristics between JDM and JPM, and between JIIM and adult IIM. RESULTS: Eighty-six juvenile patients (75 JDMs and 11 JPMs) and 283 adult patients (133 DMs and 150 PMs) were included. Compared with patients with JDM, patients with JPM were older at diagnosis, had more fever and arthritis, and were less frequently treated with disease-modifying antirheumatic drugs (these differences were not statistically significant). Compared with patients with adult DM, those with JDM presented more frequently with calcinosis (33.8% vs 6.9%, p < 0.0001) and had less severe infections (4.3% vs 23.4%, p < 0.0001), malignancies (1.3% vs 25.6%, p < 0.0001), and mortality (3.5% vs 33%, p < 0.0001). Patients with JDM were treated less frequently with azathioprine (10.8% vs 44.7%, p < 0.0001). CONCLUSIONS: Our findings confirm that JIIMs are a heterogeneous group of diseases with relevant differences compared with adult IIMs.

Severe COVID-19 in patients with immune-mediated rheumatic diseases: a stratified analysis from the SORCOM multicenter registry.

OBJECTIVES: To evaluate risk factors for severe Coronavirus Disease 2019 (COVID-19) in patients with immune-mediated rheumatic diseases, stratified by systemic autoimmune conditions and chronic inflammatory arthritis. METHODS: An observational, cross-sectional multicenter study was performed. Patients from 10 Rheumatology departments in Madrid who presented with SARS-CoV-2 infection between Feb 2020 and May 2021 were included. The main outcome was COVID-19 severity (hospital admission or mortality). Risk factors for severity were estimated, adjusting for covariates (sociodemographic, clinical and treatments), using logistic regression analyses. RESULTS: 523 patients with COVID-19 were included, among whom 192 (35.6%) patients required hospital admission and 38 (7.3%) died. Male gender, older age and comorbidities such as diabetes mellitus, hypertension and obesity were associated with severe COVID-19. Corticosteroid doses over 10 mg/day, rituximab, sulfasalazine and mycophenolate use, were independently associated with worse outcomes. COVID-19 severity decreased over the different pandemic waves. Mortality was higher in the systemic autoimmune conditions (univariate analysis, p<0.001), although there were no differences in overall severity in the multivariate analysis. CONCLUSIONS: This study confirms and provides new insights regarding the harmful effects of corticosteroids, rituximab and other therapies (mycophenolate and sulfasalazine) in COVID-19. Methotrexate and anti-TNF therapy were not associated with worse outcomes.

Advantages of telephone assistance on adherence to treatment in patients with alcohol and other addictions during the Covid19 pandemic. / Beneficios de la atención telefónica durante la pandemia covid19 en la adherencia terapéutica en pacientes con alcoholismo y otras adicciones.

The Covid19 pandemic has led to many publications about its influence on the treatment and evolution of individuals with a substance use disorder, leading to contradictory results. In this study, the adherence and abstinence rates of patients who started treatment in an Addictive Behavior Unit during the pandemic are analyzed, compared with others who attended the previous year and comparing those who were attended in person or by phone. The results indicate that during the Covid19 period, patients had greater adherence to treatment after one month of follow up and when attended to by phone. At 3 and 12 months, greater adherence was maintained, although it was not statistically significant. Regarding abstinence, the small sample size made it difficult to obtain significant differences. The conclusion is that, despite a quantitative decrease in the number of patients beginning drug treatment, in qualitative terms the pandemic led to greater adherence in the short and medium term. Telephone attention can play an important and positive role at this point, complementary to other resources and interventions.

La pandemia por covid19 ha generado muchas publicaciones acerca de su influencia en el tratamiento y evolución de personas con un trastorno por uso de sustancias, con resultados contradictorios, a veces basadas en datos y otras en inferencias indirectas de otros datos. En este trabajo se estudia la adherencia y tasas de abstinencia de pacientes que inician tratamiento en una Unidad de Conductas Adictivas durante la pandemia, respecto a otros que acudieron el año previo y comparando los que hicieron visita presencial o telefónica. Los resultados indicaron mejor adherencia al mes de seguimiento en los pacientes del periodo covid19 y en los que fueron atendidos telefónicamente. A los 3 y 12 meses se mantuvo una mejor adherencia, aunque no significativa estadísticamente. Respecto a la abstinencia, el pequeño tamaño de la muestra dificultó obtener diferencias significativas. Se concluye que la pandemia, aunque ha significado una disminución del número de inicios de tratamientos por consumo de sustancias, también ha repercutido en una mayor adherencia a corto y medio plazo. La atención telefónica puede jugar un papel importante y positivo en este aspecto, complementario a otros recursos e intervenciones.

Occupational Therapists' Perspective on the International Classification of Functioning, Disability and Health Core Sets (ICF-CS) for Schizophrenia.

IMPORTANCE: The International Classification of Functioning, Disability and Health (ICF) Core Sets (CSs) for schizophrenia are sets of ICF categories that are relevant specifically to the functioning and disability of people with schizophrenia. OBJECTIVE: To identify the problems occupational therapists commonly encounter when treating people with schizophrenia and to validate the ICF-CSs for schizophrenia from their perspective. DESIGN: Three-round Delphi study using online surveys distributed to occupational therapists worldwide. Participants were asked which problems with functioning they considered most relevant when treating people with schizophrenia. PARTICIPANTS: Occupational therapists experienced in the treatment of people with schizophrenia. MEASURES: Responses were linked to the ICF categories by two trained health professionals, and a statistical measure of agreement and κ coefficient were calculated. RESULTS: Ninety-two occupational therapists from 29 countries in all six World Health Organization regions named 2,527 meaningful concepts. After the linking process, 121 ICF categories and 31 Personal Factors were presented to the expert panel, who reached consensus (agreement of ≥75%) on 97 ICF categories and 27 Personal Factors. Consensus was reached on the 25 categories in the Brief ICF-CS for schizophrenia and 89 of the 97 categories in the Comprehensive ICF-CS for schizophrenia. CONCLUSIONS AND RELEVANCE: The ICF Core Sets for schizophrenia were validated from the perspective of occupational therapists and are potentially useful tools for clinical practice because they cover a wide variety of problems that occupational therapists deal with in interventions with people with schizophrenia. WHAT THIS ARTICLE ADDS: The ICF-CSs for schizophrenia are useful guides for describing and classifying functioning, disability, and health to aid occupational therapy intervention with people with schizophrenia. Occupational therapists are essential in the rehabilitation of this client population, and their perspective has contributed to the development and enrichment of the ICF-CSs for schizophrenia.

Circulating CD19+CD24hiCD38hi regulatory B cells as biomarkers of response to methotrexate in early rheumatoid arthritis.

OBJECTIVE: The protagonism of regulatory B cells seems to vary along the course of the disease in murine models of inflammatory conditions. Decreased numbers of circulating regulatory CD19+CD24hiCD38hi transitional (cTr) B cells have been described in patients with long-standing RA, thus our objective was to examine the frequency and evolution of cTr B cells in the peripheral blood of early RA (ERA) patients. METHODS: Freshly isolated peripheral blood mononuclear cells from 48 steroid- and DMARD-naïve ERA patients with a disease duration of <24 weeks and 48 healthy controls (HCs) were examined by flow cytometry. Co-cultures of isolated memory B cells were established with autologous T cells in the absence or presence of Tr B cells. RESULTS: As compared with HCs, ERA patients demonstrated an increased frequency of cTr B cells. cTr B cells of ERA patients and HCs displayed an anti-inflammatory cytokine profile and were able to downregulate T cell IFN-γ and IL-21 production, together with ACPA secretion in autologous B/T cell co-cultures. Basal frequencies of cTr B cells above the median value observed in HCs were associated with a good EULAR response to MTX at 12 months [relative risk 2.91 (95% CI 1.37, 6.47)]. A significant reduction of cTr B cells was observed 12 months after initiating MTX, when the cTr B cell frequency was no longer elevated but decreased, and this was independent of the degree of clinical response or the intake of prednisone. CONCLUSION: An increased frequency of regulatory cTr B cells is apparent in untreated ERA and the baseline cTr B cell frequency is associated with the clinical response to MTX at 12 months.

A systematic review of treatments for alcohol-related cognitive impairment: lessons from the past and gaps for future interventions.

Alcohol-related cognitive impairment (ARCI) is highly prevalent among patients with alcohol dependence. Although it negatively influences treatment outcome, this condition is underdiagnosed and undertreated. The aim of this systematic review is to investigate the existing evidence regarding both cognitive and pharmacological interventions for ARCI. We systematically reviewed PubMed, Scopus and Science direct databases up to May 2019 and followed the PRISMA guidelines. The quality of the studies was assessed using the Jadad Scale. Twenty-six studies were eligible for inclusion (14 referring to neuropsychological interventions and 12 to pharmacological treatments). Among neuropsychological interventions, computerised treatments, errorless learning and component method showed positive effects on working memory, memory measures and general cognitive function. On the other hand, thiamine, memantine and methylphenidate improved working memory, long-term memory and general cognitive function. Nevertheless, these studies have several limitations, such as small sample size, lack of replication of the results or low specificity of the interventions. Therefore, no gold-standard intervention can yet be recommended for clinical practice, and further research based on promising strategies (e.g. digital interventions, thiamine) is required.

Lower frequency of anti-citrullinated protein antibodies among early arthritis patients with high body mass index.

OBJECTIVES: To investigate the role of body mass index (BMI) in the phenotypic and genotypic characteristics of early arthritis patients. METHODS: We analysed the clinical and laboratory parameters from the baseline visit of patients (670 patients [78.51% women]) included in the PEARL study. The WHO definition for low weight, normal weight, overweight and obesity (BMI <18.5, 18.5-25, 25-30 or ≥30 kg/m2, respectively) was applied. Anticitrullinated protein antibodies (ACPA) were studied by ELISA and HLA-DRB1* were genotyped by sequence speci c oligonucleotide probes. The relationship between BMI classification and other variables was analysed using Kruskall-Wallis, Anova and Chi-Square tests. Then multivariate logistic regression was performed to establish the role of BMI in ACPA positivity and ordered logistic regression to establish its relationship with ACPA level. RESULTS: Among the patients studied, 255 (38.06%) were considered overweight and 136 (20.3%) obese. High BMI patients had significantly more pain perception and disability than normal weight patients, whereas no clear differences in disease activity were observed between high BMI and normal weight patients. ACPA positivity was significantly less frequent in overweight and obese patients compared to normal BMI patients. This information was confirmed by adjusting for smoking habit and the presence of shared epitope. CONCLUSIONS: Our data support the theory that high BMI patients suffer more frequently from ACPA-negative RA. Nevertheless, although no disease activity differences were observed, these patients showed higher pain and disability scores since the beginning of disease.

Two populations of circulating PD-1hiCD4 T cells with distinct B cell helping capacity are elevated in early rheumatoid arthritis.

OBJECTIVE: A novel population of B helper cells, phenotypically CD4+CXCR5-PD-1hi, has been described in the synovial tissues and peripheral blood of seropositive RA patients, and termed 'peripheral helper T' (Tph) cells. Contrary to CD4+CXCR5+PD-1hi follicular helper T (Tfh), Tph cells are not located in lymphoid organs but accumulate in inflamed tissues. Our objective was to study the frequency of circulating Tph (cTph) and circulating Tfh cell counterparts (cTfh) in patients with early RA (eRA). METHODS: Freshly isolated peripheral blood mononuclear cells from 56 DMARD-naïve eRA patients and 56 healthy controls were examined by flow cytometry. Autologous cocultures of naïve or memory B cells were established with isolated peripheral blood Tph or Tfh cells. RESULTS: Seropositive (RF+ and/or ACPA+, n = 38) but not seronegative eRA patients (n = 18) demonstrated increased frequencies and absolute numbers of cTph and cTfh cells. cTph but not cTfh cells expressed CCR2. Those eRA patients who experienced a significant clinical improvement at 12 months demonstrated a marked decrease of their cTph cell numbers whereas their cTfh cell numbers remained unchanged. Both isolated Tph and isolated Tfh cells were able to induce maturation of memory B cells, whereas only Tfh cells could differentiate naïve B cells. CONCLUSION: Two populations of PD-1hiCD4 T cells with distinct phenotype and B cell helping capacity are increased in the peripheral blood of seropositive eRA patients. Whereas cTph cells are present only in patients with an active disease, cTfh cells seem to be constitutively elevated.

The Relationship Between Religiosity and Anxiety: A Meta-analysis.

Several research studies from the USA and Western industrialized countries have reported a negative association between religiosity and anxiety. However, Arabic studies using mainly Muslim samples are limited. The objective of the present study was to apply meta-analysis statistical techniques to 10 Arabic studies of this association. All of the respondents were Arab citizens, ranging in age between 14 and 43 years, and the vast majority of them were Muslims. Religiosity and anxiety were assessed with seven different scales. In all of the studies, the administration of the scales was in small group sessions and in the Arabic language. Pearson correlation coefficients were calculated between the religiosity and anxiety scale scores. All the correlations were negative. All but one were statistically significant, ranging from - 0.16 to - 0.43. The mean effect size was - 0.22, and the impact of age and gender on the correlation was not significant. This result suggests that religiosity may affect anxiety by providing buffering and coping mechanisms.

Barriers to implement screening for alcohol consumption in Spanish hypertensive patients.

Background: Alcohol intake and hypertension (HT) are interrelated public health problems with cost-effective interventions at the primary care level that, to date, are poorly implemented. Objective: This study aims to explore the barriers to implementing alcohol interventions for people with HT in primary care. Methods: As part of the project BASIS (Baseline Alcohol Screening and Intervention Survey), an internet survey from five European countries was developed to determine the role of alcohol in the management of HT in primary care practice. The survey contained 28 core items and 7 country-specific items. We present answers from Spanish general practitioners (GPs), who were reached through the main professional and scientific societies via e-mail and asked to take the online survey. Results: In total, 867 GPs answered the survey (65.1% women, 70.4% > 30 years old). As indicated by the Alcohol Use Disorders Identification Test-C scores, 12.4% of GPs who responded were risky drinkers (21.3% of men versus 7.1% of women). GPs reported considering alcohol relatively unimportant in HT treatment, as well as a difficult condition to deal with. The three main barriers to implement screening for alcohol consumption in HT patients were the lack of time (50.0%), considering alcohol unimportant for HT (28.4%) and stigma (16.5%). Conclusions: GPs did not consider alcohol consumption a relevant factor for HT and, additionally, found it difficult to deal with alcohol problems. Some of the barriers for alcohol screening could be overcome through structural changes in the health system, such as empowering GPs to treat alcohol use disorders (rather than a single focus on implementing preventive strategies) by enhancing training in alcohol diagnosis and treatment.

EULAR definition of arthralgia suspicious for progression to rheumatoid arthritis.

BACKGROUND: During the transition to rheumatoid arthritis (RA) many patients pass through a phase characterised by the presence of symptoms without clinically apparent synovitis. These symptoms are not well-characterised. This taskforce aimed to define the clinical characteristics of patients with arthralgia who are considered at risk for RA by experts based on their clinical experience. METHODS: The taskforce consisted of 18 rheumatologists, 1 methodologist, 2 patients, 3 health professionals and 1 research fellow. The process had three phases. In phase I, a list of parameters considered characteristic for clinically suspect arthralgia (CSA) was derived; the most important parameters were selected by a three-phased Delphi approach. In phase II, the experts evaluated 50 existing patients on paper, classified them as CSA/no-CSA and indicated their level of confidence. A provisional set of parameters was derived. This was studied for validation in phase III, where all rheumatologists collected patients with and without CSA from their outpatient clinics. RESULTS: The comprehensive list consisted of 55 parameters, of which 16 were considered most important. A multivariable model based on the data from phase II identified seven relevant parameters: symptom duration <1 year, symptoms of metacarpophalangeal (MCP) joints, morning stiffness duration ≥60 min, most severe symptoms in early morning, first-degree relative with RA, difficulty with making a fist and positive squeeze test of MCP joints. In phase III, the combination of these parameters was accurate in identifying patients with arthralgia who were considered at risk of developing RA (area under the receiver operating characteristic curve 0.92, 95% CI 0.87 to 0.96). Test characteristics for different cut-off points were determined. CONCLUSIONS: A set of clinical characteristics for patients with arthralgia who are at risk of progression to RA was established.

Addressing regional disparities in pediatric oncology: Results of a collaborative initiative across the Mexican-North American border.

BACKGROUND: Cancer is emerging as a major cause of childhood mortality in low- and middle-income countries. In Mexico, cancer is the number one cause of death in children aged 5-14. Until recently, many children with cancer from Baja California, Mexico, went untreated. We reasoned that an initiative inspired by the St. Jude Children's Research Hospital (SJCRH) "twinning" model could successfully be applied to the San Diego-Tijuana border region. In 2008, a twinning project was initiated by Rady Children's Hospital, SJCRH, and the General Hospital Tijuana (GHT). Our aim was to establish a pediatric oncology unit in a culturally sensitive manner, adapted to the local healthcare system. PROCEDURE: An initial assessment revealed that despite existence of basic hospital infrastructure at the GHT, the essential elements of a pediatric cancer unit were lacking, including dedicated space, trained staff, and uniform treatment. A 5-year action plan was designed to offer training, support the staff financially, and improve the infrastructure. RESULTS: After 7 years, accomplishments include the opening of a new inpatient unit with updated technology, fully trained staff, and a dedicated, interdisciplinary team. Over 700 children have benefited from accurate diagnosis and treatment. CONCLUSIONS: Initiatives that implement long-term partnerships between institutions along the Mexican-North American border can be highly effective in establishing successful pediatric cancer control programs. The geographic proximity facilitated accelerated training and close monitoring of project development. Similar initiatives across other disciplines may benefit additional patients and synergize with pediatric oncology programs to reduce health disparities in underserved areas.

Mortality and prognostic factors in idiopathic inflammatory myositis: a retrospective analysis of a large multicenter cohort of Spain.

The present study was undertaken to assess mortality, causes of death, and associated prognostic factors in a large cohort of patients diagnosed with idiopathic inflammatory myositis (IIM) from Spain. A retrospective longitudinal study was carried out in 467 consecutive patients with IIM, identified from 12 medical centers. Patients were classified as primary polymyositis, primary dermatomyositis (DM), overlap myositis, cancer-associated myositis (CAM), and juvenile idiopathic inflammatory myopathies. A total of 113 deaths occurred (24%) after a median follow-up time of 9.7 years. In the overall cohort, the 2-, 5-, and 10-year survival probabilities were 91.9, 86.7, and 77%, respectively. Main causes of death were infections and cancer (24% each). Multivariate model revealed that CAM (HR = 24.06), OM (HR = 12.00), DM (HR = 7.26), higher age at diagnosis (HR = 1.02), severe infections (HR = 3.66), interstitial lung disease (HR = 1.61), and baseline elevation of acute phase reactants (HR = 3.03) were associated with a worse prognosis, while edema of the hands (HR = 0.39), female gender (HR = 0.39), and longer disease duration (HR = 0.73) were associated with a better prognosis. The standardized mortality ratio was 1.56 (95% CI 1.28-1.87) compared to the Spanish general population. Our findings indicate that IIM has a high long-term mortality, with an excess of mortality compared to the Spanish population. A more aggressive therapy may be required in IIM patients presenting with poor predictive factors.

Comparing a tapering strategy to the standard dosing regimen of TNF inhibitors in rheumatoid arthritis patients with low disease activity.

OBJECTIVES: The aim of this study is to compare clinical outcomes, incidence of flares and administered drug reduction between rheumatoid arthritis (RA) patients under TNF inhibitors (TNFi) tapering strategy and RA patients on standard regimen. METHODS: Two groups of RA patients on TNFi with DAS28<3.2 were compared: the tapering group (TG: 67 pts from Spain) and the control group with standard therapy regimen (CG: 77 pts from the Netherlands). DAS28 was measured at different time points: visit 0 (prior starting TNFi), visit 1 (prior to start tapering in TG and with DAS28<3.2 in TG and CG), visit 2 (6 months after visit 1), visit 3 (1 year after visit 1), visit 4 (the last visit available after visit 1) and visit-flare (visit with the worst flare between visit 1 and visit 4). RESULTS: Despite the reduction of administered drug at visit 4 in the TG (interval elongation of 32.8% in infliximab, 52.9% in adalimumab and 52.6% in etanercept), the DAS28 remained similar between groups at the end of the study (DAS28: 2.7±0.9 in TG vs. 2.5±1 in CG, p=0.1). No differences were seen in the number of patients with flares [26/67 (38.9%) in the TG vs. 30/77 (39%) in the CG, p=0.324] and only nineteen out of 136 patients (14%) had anti-drug antibodies at the end of the study. CONCLUSIONS: The tapering strategy of TNFi in RA patients result in a reduction of the drug administered, while the disease control is not worse than patients on the standard regimen.

Subsequent biologic and targeted synthetic disease modifying anti rheumatic drugs after fulfilling difficult-to-treat rheumatoid arthritis criteria: a survival analysis.

OBJECTIVES: To evaluate the survival of different biologic or targeted-synthetic disease-modifying antirheumatic drugs (b/tsDMARD) administered after fulfilling difficult-to-treat rheumatoid arthritis (D2TRA) criteria, and to assess factors related to treatment discontinuation. METHODS: Retrospective study including D2TRA patients. Drug retention of the b/tsDMARD administered after fulfilling D2TRA was assessed by Kaplan-Meier plots and the log-rank test. Cox hazard models were used to identify factors affecting treatment discontinuation. RESULTS: Of the 122 patients included, 75 maintained active treatment (61.5%) with a subsequent line after D2T compared to 47 (38.5%) who discontinued and required more successive lines of b/tsDMARDs. The median survival of the treatments was 78.3(7.6) months and the treatment after D2T with the better rate of survival was rituximab, followed by JAKi and IL6Ri, while worse survival rates were associated with abatacept and TNFi. Significant differences were noted among b/tsDMARDs (log-rank p < 0.01) and to evaluate these differences, a Cox regression was performed, taking each b/tsDMARD as a reference and comparing it with the others. DAS28 values 6-months after initiation of treatment were higher in those patients who discontinued treatment [4.4(1.2) vs 3.5(1.3), p = 0.01]. The multivariate cox regression model revealed that treatment choice after D2T [HR = 1.26(95%CI 1.06-1.05)] and lower DAS28 values at 6 months [HR = 1.49(95%CI 1.16-1.52)] were independent risk factors associated with treatment discontinuation. CONCLUSIONS: Once patients met the D2TRA criteria, the subsequent line of b/tsDMARDs with the best survival rates were rituximab, JAKi and IL6Ri. Moreover, DAS28 at 6-months of treatment after D2T was an independent risk factor for drug discontinuation. Key Points • Rituximab, IL6Ri and JAKi have better retention rates in patients after fulfilling D2TRA criteria • Clinical disease activity in the first six months after fulfillment of D2TRA criteria is an independent risk factor of subsequent treatment survival.